Experimental infection of mandarin duck with highly pathogenic avian influenza A (H5N8 and H5N1) viruses

Kang, H.M.,Lee, E.K.,Song, B.M.,Heo, G.B.,Jung, J.,Jang, I.,Bae, Y.C.,Jung, S.C.,Lee, Y.J. Elsevier Scientific Pub. Co 2017 Veterinary microbiology Vol.198 No.-

<P>A highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in poultry and wild birds in South Korea in January 2014. Here, we determined the pathogenicity and transmissibility of three different clades of 1-15 viruses in mandarin ducks to examine the potential for wild bird infection. H5N8 (Glade 2.3.4.4) replicated more efficiently in the upper and lower respiratory tract of mandarin ducks than two previously identified H5N1 virus clades (clades 2.2 and 2.3.2.1). However, none of the mandarin ducks infected with H5N8 and H5N1 viruses showed severe clinical signs or mortality, and gross lesions were only observed in a few tissues. Viral replication and shedding were greater in H5N8-infected ducks than in H5N1-infected ducks. Recovery of all viruses from control duck in contact with infected ducks indicated that the highly pathogenic H5 viruses spread horizontally through contact. Taken together, these results suggest that H5N8 viruses spread efficiently in mandarin ducks. Further studies of pathogenicity in wild birds are required to examine possible long-distance dissemination via migration routes. (C) 2016 Elsevier B.V. All rights reserved.</P>

MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer

Bae, H.J.,Jung, K.H.,Eun, J.W.,Shen, Q.,Kim, H.S.,Park, S.J.,Shin, W.C.,Yang, H.D.,Park, W.S.,Lee, J.Y.,Nam, S.W. Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.2

Background & Aims: Most common reason behind changes in histone deacetylase (HDAC) function is its overexpression in cancer. However, among HDACs in liver cancer, HDAC6 is uniquely endowed with a tumor suppressor, but the mechanism underlying HDAC6 inactivation has yet to be uncovered. Methods: Microarray profiling and target prediction programs were used to identify miRNAs targeting HDAC6. A series of inhibitors, activators and siRNAs was introduced to validate regulatory mechanisms for microRNA-221-3p (miR-221) governing HDAC6 in hepatocarcinogenesis. Results: Comprehensive miRNA profiling analysis identified seven putative endogenous miRNAs that are significantly upregulated in hepatocellular carcinoma (HCC). While miR-221 was identified as a suppressor of HDAC6 by ectopic expression of miRNA mimics in Dicer knockdown cells, targeted-disruption of miR-221 repressed cancer cell growth through derepressing HDAC6 expression. Suppression of HDAC6 via miR-221 was induced by JNK/c-Jun signaling in liver cancer cells but not in normal hepatic cells. Additionally, cytokine-induced NF-κBp65 independently regulated miR-221, thereby suppressing HDAC6 expression in HCC cells. HCC tissues derived from chemical-induced rat and H-ras12V transgenic mice liver cancer models validated that JNK/c-Jun activation and NF-κBp65 nuclear translocation are essential for the transcription of miR-221 leading to repression of HDAC6 in HCC. Conclusions: Our findings suggest that the functional loss or suppression of the tumor suppressor HDAC6 is caused by induction of miR-221 through coordinated JNK/c-Jun- and NF-κB-signaling pathways during liver tumorigenesis, providing a novel target for the molecular treatment of liver malignancies.

한우 비육에 관한 연구 1 . Methylthiouracil 첨가 및 Estradiol 17β - Cypionate 주사가 약령 모우 비육에 미치는 효과

김창기 ( C K Kim ),이택원 ( T W Lee ),김종욱 ( J W Kim ),배대식 ( D S Bae ),오선균 ( S K Oh ),조지훈 ( C H Cho ),김법회 ( B H Kim ),김상렬 ( S Y Kim ),배신석 ( S S Bae ) 한국축산학회 1971 한국축산학회지 Vol.13 No.1

This study was performed to affirm any effects of methylthiouracil and estradiol 17β-cypionate administered to young bulls for short term fattening. Eighteen bulls of Korean native breed, approximately 1.5 to 2 years of age and 260㎏ to 360㎏ in weight, were used in this study. All bulls had received a basal ration of soiling corn and concentrate made up of 55% grains, 40% brans and 5% others, in a period of 40 days. Bulls were divided into six groups as follows: group C was not treated, group M-2 received 2g of methylthiouracil per day, group M-3 received 3g of methylthiouracil per day, group EM-0 was injected intramusculary with 25㎎ of estradiol 17β-cypionate in the neck region 10 days after the beginning of the fattening period, group EM-2 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 2g of methylthiouracil per day, and group EM-3 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 3g of methylthiouracil per day. The results obtained were summarized as follows. 1. The average daily gain was for group C: 0.83㎏, group M-2: 1.07㎏, group M-3: 1.40㎏, group EM-0, 0.93㎏, group EM-2: 0.95㎏, and group EM-3: 1.18㎏. The M-3 group gained significantly(P$lt;0.05) more weight than C and EM-0 group. There were no significant differences in the average daily gain between the groups injected with estradiol 17β-eypionate and the control group. 2. The average daily concentrate intake was as follows: group C: 5.47㎏, group M-2: 5.00㎏, group M-3: 4.52㎏, group EM-0: 5.21㎏, group EM-2: 4.35㎏, and group EM-3: 4.61㎏. The consumption of concentrate was decreased by 17% in the M-3 group compared with the C group. There was no significant difference in the soiling corn intake among these groups. 3. Feed consumed for 1㎏ gain were decreased by the supplementation of methylthiouracil. The consumption of DCP for 1㎏ gain was in group C: 0.82㎏, group M-2: 0.59㎏, group M-3: 0.41㎏, group EM-0: 0.70㎏, group EM-2: 0.59㎏, and group EM-3: 0.50㎏. The amounts of TDN required were; group C: 6.57㎏, group M-2: 4.76㎏, group M-3: 3.39㎏, group EM-0: 5.67㎏, group EM-Z: 4.87㎏, and group EM-3: 4.08㎏. The consumption of DCP and TDN for 1㎏ gain in the M-3 group was about a half of that in the C group. 4. There was not any significant difference in the increase in body measurements among the various groups. 5. The average margins in the fattening period of 40 days were for group C: 2,950won, group M-2: 5,327won, group M-3: 9,158won, group EM-0: 3,310won, group EM-2: 3,623won, and group EM-3: 5,575won. The margin of group M-3 was about three times higher than that of group C. In short, this experiment demonstrated that methylthiouracil when fed to young native Korean bulls at the proper level 40 days before slaughter would bring a noticeable effect on weight gain, feed efficiency and economic advantage. There were no advantages from the simultaneous injecting estradiol 17β-cypionate with methylthiouracil. The proper supplementation level of methylthiouracil would appear to be 3g per head per day in this experiment.

An outbreak of highly pathogenic H5N1 avian influenza in Korea, 2008

Kim, H.R.,Park, C.K.,Lee, Y.J.,Woo, G.H.,Lee, K.K.,Oem, J.K.,Kim, S.H.,Jean, Y.H.,Bae, Y.C.,Yoon, S.S.,Roh, I.S.,Jeong, O.M.,Kim, H.Y.,Choi, J.S.,Byun, J.W.,Song, Y.K.,Kwon, J.H.,Joo, Y.S. Elsevier Scientific Pub. Co 2010 Veterinary microbiology Vol.141 No.3

In spite of intensive surveillance programs for the control of HPAI, an outbreak of highly pathogenic avian influenza (HPAI) H5N1 in Korea in April 2008 caused serious damage to poultry farms, as did previous outbreaks in 2003/2004 and 2006/2007. Six viruses were selected from the Korean 2008 isolates for genetic analysis, and all eight gene segments from each of the influenza viruses were sequenced. A phylogenetic analysis showed that all of the viruses were of the same virus type and that the hemagglutinin (HA) gene was clustered with that of clade 2.3.2 viruses. However, the internal and neuraminidase (NA) genes were closely related to those of the clade 2.3.4 viruses (recent human and bird isolates from Southeast Asia).

Asymmetric dibenzoylated monobenzotetraazacyclo[15]annulenenickel(II) complexes

Kim, E. H.,Kim, D. I.,Park, I. J.,Bae, Z. U.,Byun, J. C.,Na, H. G.,Park, Y. C. Gordon and Breach Science Pub 2007 Journal of coordination chemistry Vol.60 No.4

<P> The 15-membered asymmetric complexes, 3,11-di(p-Xbenzoyl)-2,4,10,12-tetramethyl-1,5,9,13-monobenzotetraazacyclo[15]annulenenickel(II), X = CH3, H, Cl, NO2 and OCH3, were synthesized and characterized. IR spectra of the benzoylated complexes showed an intense C=O stretching mode in the range 1630-1640 cm-1. Hammett plots of [image omitted]of π → π* and LMCT were linear with slopes of +0.379 and +0.339, respectively. 1H NMR signals of methyl groups showed shielding effects due to magnetic anisotropy of benzoyl groups, while other proton signals exhibited deshielding effects. 13C NMR spectra were consistent with 1H NMR. Voltammograms of complexes showed two irreversible oxidation peaks due to the ligands in the ranges +0.35 to +0.44 V and +0.74 to +0.86 V, respectively. A reduction wave involving nickel(II) was found in the range -2.50 to -2.70 V, depending on substituents on the benzoyl group. Hammett plots of the first and second oxidation potentials had linear slopes of +0.071 and +0.104, respectively. The structures of 2,4,10,12-tetramethyl-1,5,9, 13-monobenzotetraazacyclo[15]annulenenickel(II) (monoclinic, C2/c, a = 22.883(6), b = 10.358(3), c = 14.755(4) Å, &bgr; = 102.704(4)°, Z = 8, R1 [I > 2σ(I)] = 0.0295, wR2 [I > 2σ(I)] = 0.0744) and 3,11-di(p-methylbenzoyl)-2,4,10,12-tetramethyl-1,5,9,13-monobenzotetraazacyclo[15]annulenenickel(II) (orthorhombic, Pca21, a = 27.829(3), b = 10.3904(11), c = 10.4664(11) Å, Z = 4, R1 [I > 2σ(I)] = 0.0387, wR2 [I > 2σ(I)] = 0.0840) were determined using single-crystal X-ray methods.</P>

Impedance spectroscopy of Bi_3.25La_0.75Ti₃O₁₂ ceramics above and below ferroelectric transition temperatures

Park, J H,Bae, J S,Choi, B C,Jeong, J H Institute of Physics Publishing Ltd. 2007 Journal of Physics. D, Applied Physics Vol.40 No.2

<P>The complex impedance of Bi<SUB>3.25</SUB>La<SUB>0.75</SUB>Ti<SUB>3</SUB>O<SUB>12</SUB> ceramic was measured over a temperature range 50–600 °C at several frequencies. The complex capacitance anomaly of the ferroelectric phase transitions was observed near <I>T</I><SUB>c</SUB> = 395 °C. Remarkable capacitance dispersion of the complex capacitance was found above 250 °C. The complex impedance spectra above 250 °C were fitted by the superposition of two Cole–Cole types of relaxations. The fast component in the higher frequency region may be due to the orientational grain–grain boundary, and the slow component in the lower frequency region is interpreted as the formation and migration of ions at the surface or electrode/crystal interfacial polarization. We found two different conduction mechanisms that have different activation energies: <I>E</I> ∼ 0.33 eV above <I>T</I><SUB>c</SUB> and <I>E</I> ∼ 0.44 eV below <I>T</I><SUB>c</SUB> in the high-frequency regions, and <I>E</I> ∼ 0.32 eV above <I>T</I><SUB>c</SUB> and <I>E</I> ∼ 0.57 eV below <I>T</I><SUB>c</SUB> in the low-frequency regions.</P>

Carbenoxolone prevents the development of fatty liver in C57BL/6-Lep ^ob/ob mice via the inhibition of sterol regulatory element binding protein-1c activity and apoptosis

Dal Rhee, S.,Kim, C.H.,Seon Park, J.,Hoon Jung, W.,Bum Park, S.,Youn Kim, H.,Hwan Bae, G.,Jan Kim, T.,Young Kim, K. North-Holland ; Elsevier Science Ltd 2012 european journal of pharmacology Vol.691 No.1

Carbenoxolone is the 3-hemisuccinate of glycyrrhetinic acid, the active principal of licorice (Glycyrrhiza glabra). It was reported that carbenoxolone improved glucose tolerance with increased insulin sensitivity in mice with high fat diet-induced obesity. In the present study, we elucidated the protective effect of carbenoxolone in fatty liver animal models of C57BL/6-Lep<SUP>ob/ob</SUP> mice through inhibition of hepatic lipogenesis and apoptosis. In addition, the potential mechanisms by which carbenoxolone could exert such protection were elucidated. Carbenoxolone was daily administrated by gavage for 28 days in C57BL/6 and C57BL/6-Lep<SUP>ob/ob</SUP> mice. Carbenoxolone prevented the plasma triglyceride and free fatty acid accumulation associated with the reduction of the expression of sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase and acethyl-CoA carboxylase in the livers of C57BL/6-Lep<SUP>ob/ob</SUP> mice. Carbenoxolone also prevented hepatic injury through anti-apoptotic action in the livers of C57BL/6-Lep<SUP>ob/ob</SUP> mice, accompanied by increased Bcl-2 expression and suppressed Bax and cytochrome c expression. As a mechanism, increased inflammatory cytokine expressions were inhibited by carbenoxolone in the fatty livers of C57BL/6-Lep<SUP>ob/ob</SUP> mice. Furthermore, carbenoxolone inhibited free fatty acid (oleate/palmitate) induced reactive oxygen species formation and reversed free fatty acid induced mitochondrial membrane depolarization in HepG2 cells. Carbenoxolone prevents the development of fatty liver by inhibiting sterol regulatory element binding protein-1c expression and activity with an anti-apoptotic mechanism via the inhibition of inflammatory cytokine and reactive oxygen species formation in the livers of C57BL/6-Lep<SUP>ob/ob</SUP> mice. It is suggested that carbenoxolone prevents the development and progression of fatty liver disease in patients with insulin resistance.

Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice

Yu, S.J.,Bae, S.,Kang, J.S.,Yoon, J.H.,Cho, E.J.,Lee, J.H.,Kim, Y.J.,Lee, W.J.,Kim, C.Y.,Lee, H.S. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.762 No.-

<P>Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin Con bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA) induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh BAT cells were treated with bile acid, apoptosis was induced by endoplasmic retiiculum stress related JNK activation but vitamin C attenuated bile acid induced hepatocyte apoprosis in vitro. In our in vivo experiments. LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. (C) 2015 Elsevier B.V. All rights reserved.</P>

Enhanced anti-tumor efficacy and safety profile of tumor microenvironment-responsive oncolytic adenovirus nanocomplex by systemic administration

Choi, J.W.,Dayananda, K.,Jung, S.J.,Lee, S.H.,Kim, D.,Hu, J.,Bae, Y.H.,Yun, C.O. Elsevier BV 2015 ACTA BIOMATERIALIA Vol.28 No.-

Oncolytic adenovirus (Ad) holds great promise as a potential gene therapy for cancer. However, intravenously administered Ad may encounter difficulties due to unfavorable host responses, non-specific interactions, and the heterogeneity of the tumor cell population. As an approach to combine the advantages of oncolytic Ad and synthetic polymers and to address the associated difficulties, Ad was physically complexed with a pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine) (mPEG-b-pHis). The in vitro transduction efficiency at an acidic extracellular pH was remarkably enhanced in cancer cells when treated with the Ad expressing green fluorescent protein (GFP) coated with mPEG-b-pHis (c-dE1/GFP) as compared to that of naked Ad (n-dE1/GFP). Time-lapse total internal reflection fluorescence microscopic imaging revealed a significantly enhanced cellular uptake rate of c-dE1/GFP at acidic tumor pH when compared with that at neutral pH or naked cognate Ad (n-dE1/GFP). In addition, c-dE1/GFP remained relatively stable in human serum-containing media, and considerably reduced both the innate and adaptive immune response against Ad. Moreover, the therapeutic efficacy and survival benefit of mPEG-b-pHis-complexed oncolytic Ad (c-H5mT/Luc) by systemic treatment was significantly enhanced compared to that with naked oncolytic Ad (n-H5mT/Luc) in both coxsackie and adenovirus receptor-positive and -negative tumors. Whole-body bioluminescence imaging showed 7.3-fold higher luciferase expression at the tumor site and 23.0-fold less luciferase expression in liver tissue for c-H5mT/Luc relative to that for naked oncolytic Ad (n-H5mT/Luc). Considering the heterogeneity of tumor tissue, these results are important for guiding the development of more potent and specific treatment of devastating metastatic cancers using this viral system. Statement of significance: Although adenoviral systems have shown considerable promise and undergone extensive evaluation attempts to specifically target Ad vectors to cancer cells have met limited success. This shortcoming is due to the strong immune response stimulated by Ad and the hepatotoxicity of the viral particles. To overcome restricted vector issues, we generated Ad/mPEG-b-pHis for tumor microenvironment-targeting hybrid vector systems, an oncolytic Ad coated with a pH-responsive polymer, mPEG-b-pHis. The Ad/mPEG-b-pHis exhibited pH-dependent transduction efficiency and cancer-cell killing effects. Moreover, systemic administration of oncolytic Ad/mPEG-b-pHis led to marked suppression of tumor growth and tumor-specific viral replication. Ad successfully avoided the innate and adaptive immune responses and liver accumulation with the help of mPEG-b-pHis on its surface.

Single-tube nested PCR assay for the detection of avian botulism in cecal contents of chickens

Jang, I.,Lee, J.I.,Kwon, Y.K.,Kang, M.S.,Kim, H.R.,Park, J.Y.,Lee, S.H.,Lee, H.S.,Bae, Y.C. Academic Press 2015 Anaerobe Vol.35 No.2

This paper describes a novel diagnostic method for the detection of avian botulism caused by Clostridium botulinum type C and C/D, using single-tube nested PCR assay. This assay was developed to overcome the disadvantages of bioassays used in experiments with mice. Three primer pairs including an antisense primer were designed to target the N-terminal of the toxin gene from C. botulinum types C and C/D. The specificity of the PCR assay was confirmed by using 33 bacterial strains and chicken cecal contents from farms that experienced botulism outbreaks. The detection limit for purified DNA was 1.1 fg/μl, and for bacterial spores was 4.3 spores/200 mg of cecal contents. While checking for specificity of the PCR assay, the reactions with the templates form C. botulinum type C and C/D which were tested became positive, but the rest of the reactions turned negative. However, the results for all clinical samples (n = 8) were positive. The PCR assay results for cecal samples obtained from 300 healthy chickens (150 Korean native chickens and 150 broilers) were all negative. This assay is rapid and straightforward and evades ethical issues associated with mouse bioassay. Moreover, it is more economical than real-time PCR.